Despite advances of the last several years, treatments for HIV-1 infection and its complications are of limited benefit and duration. Reasons for the limited success of available drugs include the emergence of drug resistance, the development of dose- limiting toxicities, progressive increase in virus load, and progressive immunologic decline in the host. Nevertheless, it is essential to pursue clinical trials in individuals infected with HIV to test potentially useful drugs and because these trials offer the opportunity to examine the pathogenesis of HIV infection and disease progression. This application is a proposal for continued funding of the Adult AIDS Clinical Trials Unit (ACTU) at the University of Colorado Health Sciences Center in Denver, Colorado. We propose to continue enrolling HIV-infected individuals at all stages of disease into Phase I-III clinical trials to study the pathogenesis and treatment of HIV-1 infection and related opportunistic diseases. Specific emphasis will be placed on exploring the viral and immunologic basis for the pathogenesis of HIV disease in the context of experimental antiretroviral and immune-based therapies for HIV-1 infection. In addition, investigators from the Colorado ACTU will play important leadership roles in the AIDS Clinical Trials Group as a whole.